This Phase I proposal is a collaborative, multi-disciplinary effort involving researchers from TPL, Inc. (Albuquerque, New Mexico) and the Department of Bioengineering at the University of Washington. Our objective is to explore a new generation of miniature optical imaging probes for high-resolution intraluminal imaging of neoplasia at early stages. Development of a technology that enables in vivo imaging of biological tissues at or near cellular level in real time could permit diagnosis of neoplasia at early stages and precision guidance of biopsy. Optical coherence tomography (OCT) and confocal microscopy are capable of real-time imaging of biological tissues at or near cellular level, functioning in a form of "optical biopsy" but without the need for tissue removal. In vivo and endoscopic applications of OCT and confocal microscopy require a scanning miniature probe for real-time imaging and a mechanism for real-time focus tracking in order to maintain a high transverse resolution at varying depths. The proposed imaging probe integrates beam delivery, collection, focusing, and fast transverse scanning into a highly compact single unit. Unlike conventional endoscopic imaging probes, the proposed miniature probe performs rapid transverse beam scanning, which enables a new image acquisition scheme to achieve real-time-focus tracking and real-time ultrahigh-resolution optical coherence tomographic imaging in the forward direction. The specific aim of this Phase I exploratory study is to develop an extremely compact, rapid scanning, forward-imaging probe based on a novel fiber-optic resonant scanner and cutting-edge micro imaging optics. The imaging probe can integrate endoscopic OCT with confocal microscopy to achieve ultrahigh-resolution imaging in real time. A successful Phase I study will warrant further relevant technology development refinement as well as pre-clinical feasibility investigations planned for Phase II. If both Phase I and II are successful, this technology will lead to a new generation of miniature imaging devices for high-resolution, non-invasive optical biopsy of neoplasia at or near cellular level in vivo and in real time.